Molecular Mechanisms Underlying Human Somatic Cell Reprogramming to Generate Induced Pluripotent Stem Cells

The discovery by Yamanaka and Thomson has opened a “new era” for biology and regenerative medicine. They showed that by expressing four transcription factors in somatic cells, these cells can be reprogrammed to induced pluripotent stem cells (iPSCs) similar to embryonic stem cells and can give rise to almost every cell type in the human body. The creation of these special cells was major ground-breaking work in cell biology and opened the path for providing unprecedented access to patient-specific iPS cells for drug screening, disease modeling and cell therapy applications. Beside therapeutic issues, iPS cell technology opens the door for broader research on human pluripotent cells because ethical limitations are lifted with iPS cells as compared to hES cells. Therefore, it is not surprising that the methods for generating iPSCs have significantly evolved over the past few years. We are now able to convert essentially any somatic cell type into iPSCs with increased efficiency and at higher quality when compared to ESCs. Despite these advances, the molecular events occurring during various stages of reprogramming remain largely unknown. In this review we will discuss the current understanding of molecular mechanisms underlying human somatic cell reprogramming to generate induced pluripotent stem cells.